Date of Award

5-2005

Degree Type

Thesis

Degree Name

MS Biology

Department

Biology

Advisor

Allan Blake

Committee Member

Linda Hsu

Committee Member

Jane Ko

Committee Member

Sulie Chang

Keywords

Somatostatin, Intracellular Signaling, Human Bronchial Smooth Muscle Cells

Abstract

Somatostatin (somatotropin release inhibitory factor; SRIF), is an endogenous peptide family that controls cellular secretion and proliferation. While SRIF's cognate receptors and associated actions have been clearly identified in a range of tissues, such as the endocrine, gastrointestinal and immune systems, a role in human lung physiology remains unknown. Using primary human bronchial smooth muscle cells (hBSMC) as a model for studying SRIF's actions, we have investigated whether SRIF receptors are present and functional in human bronchial smooth muscle. Reverse transcriptase- polymerase chain reaction (RT-PCR) analysis ofhBSMC total mRNA demonstrated the presence of the sst, receptor subtype, providing a molecular target for SRIF action. SRIF's functional effects on intracellular signaling were confirmed by Western blotting with phospho-specific antibodies for the extracellular regulated kinases 1/2 (ERKl/2). Using a nonpeptidyl sst, selective agonist, L-779,976, we demonstrated an acute inhibition (50 ± 5%) of basal ERKl/2 phosphorylation. In addition, L-779,976-treated hBSMC cell membranes showed a 2.4-fold increase in tyrosine phosphatase activity, which was abolished by the selective tyrosine phosphatase inhibitor sodium vanadate. Furthermore, a 48 h treatment with 100 nM L-779,976 suppressed hBSMC proliferation by 30%. Taken together, our results show that the hBSMC is a direct target of SRIF' s antiproliferative activity. We propose that SRIF's actions in controlling lung smooth muscle cell proliferation could prove therapeutically useful in chronic asthma where inappropriate hBSMC proliferation plays a role.

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